A physiologically based toxicokinetic model for dietary uptake of hydrophobic organic compounds by fish: I. Feeding studies with 2,2',5,5'-tetrachlorobiphenyl.
(1/20)
A physiologically based toxicokinetic (PBTK) model was developed to describe dietary uptake of hydrophobic organic compounds by fish. The gastrointestinal (GI) tract was modeled using four compartments corresponding to the stomach, pyloric ceca, upper intestine, and lower intestine, and the lumenal volume of each compartment was allowed to change in time as a function of bulk flow down the GI tract and (for the pyloric ceca and upper intestine) nutrient uptake. The model was developed using data from rainbow trout that were fed a single meal of 60-day-old fathead minnows contaminated with [UL-(14)C] 2,2',5,5'-tetrachlorobiphenyl ([(14)C] PCB 52). Chemical partitioning coefficients for the gut contents and tissues were adjusted to account for changes in chemical affinity associated with uptake of dietary lipid. Permeability constants for the absorbing gut segments were then fitted by modeling to measured [(14)C] PCB 52 concentrations in gut contents and tissues. The model accurately describes observed patterns of gastric evacuation and bulk flow of digesta, the concentration time course for [(14)C] PCB 52 in contents and tissues of the GI tract, and [(14)C] PCB 52 distribution to other major tissues. Most of the [(14)C] PCB 52 was taken up in the pyloric ceca and upper intestine during the period of peak lipid absorption. It is concluded, however, that a kinetic limitation acting along the entire length of the GI tract resulted in a chemical disequilibrium between feces and tissues of the lower intestine. (+info)
Systemic spindle-cell proliferative disease in broiler chickens.
(2/20)
The major organs and tissues of 24 broiler chickens (70 or 71 days old) suspected of spindle-cell proliferative disease (SPD) because of showing the tumorous lesions distributed throughout the body at meat inspection were collected for histopathological and immunohistochemical examination. Macroscopically, liver, spleen and cecal tonsil showed severe enlargement and white nodules or plaques were observed in the liver, spleen, kidney, intestine and bone marrow of the femur. All chickens were diagnosed with SPD based on the histopathological examination. The lesions of SPD were observed in the liver, spleen, kidney, heart, lung, pancreas, proventriculus, gizzard, duodenum, jejunum, ileum, rectum, cecal tonsil, bursa of Fabricius, bone marrow of the femur and skin. Hemangioma was observed in the lung of 1 bird. Eight 1-day-old specific pathogen-free chicks were inoculated intraperitoneally with 0.25 ml of a 20% homogenate of the affected spleens of three naturally occurring cases. One inoculated bird, necropsied at 10 weeks of age, macroscopically had a white nodule in the kidney and histopathologically had spindle-cell proliferative lesions, a pattern similar to that seen in the naturally occurring cases, in the liver, spleen, kidney, heart, lung, pancreas, proventriculus, duodenum, cecal tonsil and bone marrow of the femur, and was diagnosed with SPD. Immunohistochemically, significant positive reactions with a rabbit antiserum against avian leukosis virus antigens were detected in all spindle cells in the proliferative lesions of all examined SPD cases and in tumor cells of the hemangioma of a field case. (+info)
Significance of salicylate intolerance in diseases of the lower gastrointestinal tract.
(3/20)
Salicylate intolerance is defined as a nonspecific antigen-induced pseudo-allergic hypersensitivity reaction which can occur upon contact of an organism with salicylic acid, its derivatives or other related organic or inorganic acids of similar chemical structure. Since the effects of nonsteroidal anti-inflammatory drugs (NSAID) intolerance are by no means always severe or life-endangering but may just as well present as oligosymptomatic or local disorders (e.g. abdominal pain, diarrhea, we decided to evaluate the characteristics of patients with salicylate intolerance on the basis of gastroenterological case material of Medical Department I of Erlangen University. On the basis of the findings from the Erlangen interdisciplinary data register of chronic inflammatory gastrointestinal disease, the signs and symptoms of NSAID intolerance were found to constitute a diagnosis of great practical import to clinical medicine (allergology, dermatology, immunology, other disorders etc.) including gastroenterology. For approx. 2-7% of all patients with inflammatory bowel syndrome and food allergies this poses a new diagnostic and therapeutic challenge which may concern physicians from any of the disciplines involved. When presented with patients with chronic active disease who are suffering from these symptoms one should, therefore, in future give greater thought to the possibility of salicylate intolerance, all the more as there are meaningful dietetic, diagnostic and therapeutic options available for these persons. (+info)
Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.
(4/20)
BACKGROUND: Lower gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) are much more poorly characterized than upper gastrointestinal effects. AIM: To determine if NSAIDs increase lower gastrointestinal adverse effects and if the risk with non-selective NSAIDs is greater than with cyclooxygenase-2-selective inhibitors (coxibs). METHODS: Computerized databases were searched to identify studies of NSAID use reporting on lower gastrointestinal integrity (e.g. permeability), visualization (e.g. erosions, ulcers) and clinical events. RESULTS: Designs in 47 studies were randomized (18), case-control (14), cohort (eight) and before-after (seven). Non-selective-NSAIDs had significantly more adverse effects vs. no NSAIDs in 20 of 22 lower gastrointestinal integrity studies, five of seven visualization studies, seven of 11 bleeding studies (OR: 1.9-18.4 in case-control studies), two of two perforation studies (OR: 2.5-8.1) and five of seven diverticular disease studies (OR: 1.5-11.2). Coxibs had significantly less effect vs. non-selective-NSAIDs in three of four integrity studies, one endoscopic study (RR mucosal breaks: 0.3), and two randomized studies (RR lower gastrointestinal clinical events: 0.5; haematochezia: 0.4). CONCLUSIONS: An increase in lower gastrointestinal injury and clinical events with non-selective-NSAIDs appears relatively consistent across the heterogeneous collection of trials. Coxibs are associated with lower rates of lower gastrointestinal injury than non-selective-NSAIDs. More high-quality trials are warranted to more precisely estimate the effects of non-selective-NSAIDs and coxibs on the lower gastrointestinal tract. (+info)
brachyenteron is necessary for morphogenesis of the posterior gut but not for anteroposterior axial elongation from the posterior growth zone in the intermediate-germband cricket Gryllus bimaculatus.
(5/20)
In the long-germband insect Drosophila, all body segments and posterior terminal structures, including the posterior gut and anal pads, are specified at the blastoderm stage. In short- and intermediate-germband insects, however, posterior segments are sequentially produced from the posterior growth zone, a process resembling somitogenesis in vertebrates, and invagination of the posterior gut starts after anteroposterior (AP) axial elongation from the growth zone. The mechanisms underlying posterior segmentation and terminal patterning in these insects are poorly understood. In order to elucidate these mechanisms, we have investigated the roles of the Brachyury/brachyenteron (Bra/byn) homolog in the intermediate-germband cricket Gryllus bimaculatus. Loss-of-function analysis by RNA interference (RNAi) revealed that Gryllus byn (Gb'byn) is not required for AP axial elongation or normal segment formation, but is required for specification of the posterior gut. We also analyzed Gryllus caudal (Gb'cad) RNAi embryos using in situ hybridization with a Gb'byn probe, and found that Gb'cad is required for internalization of the posterior gut primordium, in addition to AP axial elongation. These results suggest that the functions of byn and cad in posterior terminal patterning are highly conserved in Gryllus and Drosophila despite their divergent posterior patterning. Moreover, because it is thought that the progressive growth of the AP axis from the growth zone, controlled by a genetic program involving Cdx/cad and Bra/byn, might be ancestral to bilaterians, our data suggest that the function of Bra/byn in this process might have been lost in insects. (+info)
Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice.
(6/20)
We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P<0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-alpha, interleukin-1beta [IL-1beta], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa. (+info)
Radiologic diagnosis and management of acute lower gastrointestinal bleeding.
(7/20)
In patients with acute lower gastrointestinal bleeding, colonoscopy is the initial test of choice. But when colonoscopy gives indeterminate results or cannot be performed, either radionuclide imaging or angiography is indicated. (+info)
Cost-effectiveness analysis of subtraction scintigraphy in patients with acute lower gastrointestinal tract hemorrhage.
(8/20)
(99m)Tc-labeled red blood cell scintigraphy is a powerful detection and localization tool that may be confounded by false-positive and false-negative findings. Subtraction scintigraphy has been used in the evaluation of acute lower gastrointestinal tract hemorrhage (LGIH) to reduce the impact of interpretive confounders. The aim of this investigation was to evaluate the cost-effectiveness of the addition of subtraction scintigraphy in the evaluation of patients with acute LGIH. METHODS: The clinical phase of this research was a retrospective clinical study with a repeated-measures design including randomized control and experimental groups. A total of 49 patient studies were included in the sample. Studies were randomized and interpreted by 4 independent physicians. Decision-tree analysis was used to model direct costs and the potential risks of procedures for 2 diagnostic strategies for patients with acute LGIH: conventional scintigraphy alone and conventional scintigraphy combined with subtraction scintigraphy. The transition probabilities (or branching fraction at each decision node) for scintigraphy were based on the clinical results of this investigation. All other transition probabilities were derived from previously cited data. RESULTS: Combining subtraction techniques with conventional scintigraphy reduced the overall costs of procedures for patients with acute LGIH by $74 per patient and reduced deaths by 17.6% and complications by 15.7%. For conventional scintigraphy alone, 8.8% of patients presenting for scintigraphic evaluation of acute LGIH would undergo unnecessary angiograms, and 2.8% would have unnecessary surgery. These figures were reduced to just 5.4% and 1.8%, respectively, with the addition of subtraction scintigraphy. CONCLUSION: The use of subtraction scintigraphy as an adjunct to conventional scintigraphy for patients with acute LGIH may provide both cost and outcome benefits. (+info)